Integration of structural dynamics and molecular evolution via protein interaction networks: A new era in genomic medicine

Avishek Kumar, Brandon M. Butler, Sudhir Kumar, S. Banu Ozkan

Research output: Contribution to journalReview articlepeer-review

17 Scopus citations

Abstract

Sequencing technologies are revealing many new non-synonymous single nucleotide variants (nsSNVs) in each personal exome. To assess their functional impacts, comparative genomics is frequently employed to predict if they are benign or not. However, evolutionary analysis alone is insufficient, because it misdiagnoses many disease-associated nsSNVs, such as those at positions involved in protein interfaces, and because evolutionary predictions do not provide mechanistic insights into functional change or loss. Structural analyses can aid in overcoming both of these problems by incorporating conformational dynamics and allostery in nSNV diagnosis. Finally, protein-protein interaction networks using systems-level methodologies shed light onto disease etiology and pathogenesis. Bridging these network approaches with structurally resolved protein interactions and dynamics will advance genomic medicine.

Original languageEnglish (US)
Pages (from-to)135-142
Number of pages8
JournalCurrent Opinion in Structural Biology
Volume35
DOIs
StatePublished - Dec 1 2015

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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